Optimal prophylactic para-aortic radiotherapy in locally advanced cervical cancer: anatomy-based versus margin-based delineation

Abstract

ObjectivePrecise delineation of the para-aortic nodal region is critical for the optimal therapeutic ratio of prophylactic para-aortic radiotherapy. We aimed to evaluate the para-aortic control and patient-reported gastrointestinal toxicity in patients with locally advanced cervical cancer who received anatomy-based or margin-based prophylactic para-aortic radiotherapy.MethodsWe analyzed 160 patients with locally advanced cervical cancer who received prophylactic extended-field radiotherapy between January 2014 and November 2019 at two tertiary centers. Para-aortic nodal regions were delineated based on the anatomic principle-based atlas or marginal expansion from the aorta and inferior vena cava. The Patient-Reported Outcome version of the Common Terminology Criteria for Adverse Events was used to assess acute gastrointestinal toxicity, and a score of ≥3 was defined as severe gastrointestinal toxicity.ResultsSeventy-six (47.5%) and 84 (52.5%) patients received anatomy-based and margin-based prophylactic para-aortic radiotherapy, respectively. The median follow-up was 40.1 months (IQR 25.5–58.9). Para-aortic nodal failures occurred in one (1.3%) patient in the anatomy-based para-aortic radiotherapy group and in one (1.2%) patient in the margin-based para-aortic radiotherapy group (p=1.00). There was no in-field or marginal para-aortic nodal failure. The 3-year para-aortic recurrence-free survival for anatomy-based and margin-based para-aortic radiotherapy was 98.6% and 98.8%, respectively (p=0.94). Patients who received anatomy-based para-aortic radiotherapy reported less severe acute gastrointestinal toxicity than those who received margin-based para-aortic radiotherapy (13.2% vs 29.8%, p=0.01). A comparison of gastrointestinal toxicities showed that patients who received anatomy-based para-aortic radiotherapy reported significantly less severe gastrointestinal toxicity than those who received margin-based para-aortic radiotherapy in terms of frequency of diarrhea (7.9% vs 20.2%, p=0.03), severity of abdominal pain (3.9% vs 14.3%, p=0.03), and interference of abdominal pain (2.6% vs 11.9%, p=0.03).ConclusionAnatomy-based prophylactic para-aortic radiotherapy achieved excellent para-aortic control and a lower incidence of severe patient-reported gastrointestinal toxicity. These findings suggest that anatomy-based delineation optimizes clinical outcomes of prophylactic para-aortic radiotherapy in locally advanced cervical cancer.

Impact of reduced margin pelvic radiotherapy on gastrointestinal toxicity and outcome in gynecological cancer

“…Comparing our physician-graded acute GI toxicity with those studies, the proportion of patients with any grade ≥ 2 acute GI toxicity was similar in the RTOG pelvic radiotherapy group, but lower in the reduced margin pelvic radiotherapy group [5] , [6] . Furthermore, we evaluated the effect of reduced margin pelvic radiotherapy using PRO-CTCAE, because patient-reported outcomes can provide a more accurate assessment of treatment-related toxicity [15] , [16] , [17] , [18] , [19] . The proportion of patients who reported frequent diarrhea was 33.7% in the RTOG-1203 trial and 24.2% among our patients who received RTOG pelvic radiotherapy, but a lower proportion of patients received reduced margin pelvic radiotherapy (10.8%).…”

“…Since 2014, the Patient-Reported Outcome version of the CTCAE (PRO-CTCAE) questionnaire was also used to assess acute GI toxicity in our clinical practice. The questionnaire included questions on abdominal pain (severity, frequency, and interference with daily activities) and the frequency of diarrhea [14] , [15] , [16] . Patients scored toxicity on a 5-point Likert scale, with 0 indicating none, not at all, and never.…”

Controversies in the Staging of Patients with Locally Advanced Cervical Cancer

“…In a retrospective study that included 160 patients with locally advanced cervical cancer who received prophylactic extended-field para-aortic radiation therapy, the para-aortic nodal failure rate was comparable between anatomybased (n = 76) and margin-based (n = 84) approaches (1.3% vs. 1.2%). However, the anatomy-based approach was associated with less severe acute gastrointestinal toxicity (13.2% vs. 29.8%, p = 0.01) [41]. Improved delineation methods for the para-aortic area when delivering prophylactic extended-field radiation therapy result in significantly decreased radiation exposure of the second and third portion of the duodenum [42].…”